Factors adversely affecting the function of the gastrointestinal system in humans are exceedingly varied in their nature. Such disorders may arise in the upper or lower gastrointestinal tracts or both. There is a broad range of causes of gastrointestinal disorders, including genetic, physiological, environmental, and psychogenic factors. Accordingly, the diagnosis and management of these disorders can be exceptionally difficult. A detailed discussion of gastrointestinal tract functions, disorders, causes, and treatments can be found in Spiro, Clinical Gastroenterology (3d. edition 1983).
Among the chronic disorders of the upper gastrointestinal tract are those which fall under the general categories of gastritis and peptic ulcer disease. (The upper gastrointestinal tract as used herein is defined as including the esophagus, the stomach, the duodenum and the jejunum.) Gastritis is, by definition, typified by an inflammation of the stomach mucosa. In practice, though, the disorder is manifested by a broad range of poorly-defined, and heretofore inadequately treated, symptoms such as indigestion, "heart burn", dyspepsia and excessive eructation. A general discussion of gastritis appears in B. J. Marshall and J. R. Warren, "Unidentified Curved Bacilli in the Stomach of Patients with Gastritis and Peptic Ulceration", The Lancet, (1984), pp. 1311-1315, and in R. Greenlaw, et al., "Gastroduodenitis, A Broader Concept of Peptic Ulcer Disease", Digestive Diseases and Sciences, Vol. 25 (1980), pp. 660-672.
Peptic ulcers are lesions of the gastrointestinal tract lining, characterized by loss of tissue due to the action of digestive acids and pepsin. It has been generally held that peptic ulcers are caused either by gastric hypersecretion, or (more often) by decreased resistance of the gastric lining to digestive acids and pepsin. The medical literature is replete with methods for treating ulcers, including modification of the diet, surgical removal of the lesions, and the use of drugs. Such drugs include; antacids, which serve to counteract excess gastric secretions; anticholinergics, which reduce acid secretion; H.sub.2 antagonists, which also block the release of gastric acids; prostaglandins, which increase the resistance of the gastric lining to digestive fluids, and may also inhibit acid secretion; prokinetic agents, which enhance gastrointestinal tract motility; and compositions which form protective barriers over gastric lesions. Prescription and non-prescription drug therapies are generally described in Garnet, "Antacid Products", Handbook of Non-prescription Drugs, 7th edition (1982), Chapter 3.
Regardless of the particular drug composition used in treating gastrointestinal disorders, such as gastritis or peptic ulcer disease, the treatment is often imprecise and incomplete. Actual "cures", i.e., successful treatment resulting in total remission of disease, are very often not effected. See A. J. McLean, et al., "Cyto-protective Agents and Ulcer Relapse", 142 The Medical Journal of Australia, Special Supplement S25-S28 (1985). Furthermore, many conventional treatments may render subject hypochlorhydric (i.e., with low levels of hydrochloric acid in the stomach) which may predispose them to other disorders, e.g., gastrointestinal infection, halitosis, and gastric carcinomas.
Nitrofurantoin is a well-known antibacterial compound and has been used extensively as an active ingredient in antibacterial pharmaceutical compositions. See, for example, Mintzer, S., E. R. Kadison, W. H. Shlaes & O. Felsenfeld, "Treatment of Urinary Tract Infections with a New Antibacterial Nitrofuran", Antibiotics & Chemotherapy, Vol. 3, No. 2 (Feb., 1953), pp. 151-157; Richards, W. A., E. Riss, E. H. Kass & M. Finland, "Nitrofurantoin-Clinical and Laboratory Studies in Urinary Tract Infections", Archives of Internal Medicine, Vol. 96 (1955), pp. 437-450; Eudy, W. W., "Correlations Between In Vitro Sensitivity Testing and Therapeutic Response in Urinary Tract Infections", Urology, Vol. II, No. 5 (Nov., 1973), pp. 519-587; Bush, I. M., W. I. Metzger, I. Garlovsky, R. B. Bush, R. J. Ablin & N. Sadoughi, "Urinary Tract Infection-Antibacterial Susceptibility Patterns", Urology, Vol. III, No. 6 (Jun., 1974), pp. 697-700; Dickey, L., "A Comparison of the In Vitro Effectiveness of Nitrofurantoin and Five Antibiotics Against Bacteria from Urinary Tract Infections", American Journal of Medical Technology, (Sept.-Oct., 1961), pp. 273-279; Karmali, M. A., S. DeGrandis & P. C. Fleming, "Antimicrobial Susceptibility of Campylobacter jejuni with Special Reference to Resistance Patterns of Canadian Isolates", Antimicrobial Agents and Chemotherapy, Vol. 19, No. 4 (1981), pp. 593-597. allergic response) commensurate with a reasonable benefit/risk ratio when used in the manner of this invention. The specific "safe and effective amount" will, obviously, vary with such factors as the particular condition that is being treated, the physical condition of the patient, the nature of concurrent therapy (if any), and the specific formulations employed in the present invention. Specifically, the processes of the present invention, for the treatment and prophylaxis of a human or lower animal subject having an infectious gastrointestinal disorder, comprise the step of administering to said subject a safe and effective amount of nitrofurantoin.
As used herein, "infectious gastrointestinal disorder" encompasses any disease or other disorder of the upper gastrointestinal tract of a human or lower animal which is caused or mediated by Campylobacter-like (renamed Helicobacter) organisms (herein "CLO"), e.g., Campylobacter pyloridis (renamed Helicobacter pylori). Such CLO include those described in J. R. Warren and B. J. Marshall, "Unidentified Curved Bacilli on Gastric Epithelium in Active Chronic Gastritis", The Lancet, (1983), pp. 1273-1275, incorporated by reference herein, and G. Kasper and N. Dickgiesser, "Isolation from Gastric Epithelium of Campylobacter-like Bacteria that are Distinct from `Campylobacter Pyloridis`", The Lancet, (1985), pp. 111-112. Such infectious gastrointestinal disorders include, for example: CLO-mediated disorders not manifested by presence of ulcerations in the gastric mucosa (herein "non-ulcerative gastrointestinal disorder"), including chronic or atrophic gastritis, non-ulcer dyspepsia, esophogeal reflux disease and gastric motility disorders; and "peptic ulcer disease", i.e., CLO-mediated gastric, duodenal, and jejunal ulcers.
As used herein, "administering" refers to any method which, in sound medical practice, delivers the compounds or compositions used